Estimate the incubation period of coronavirus 2019 (COVID-19).

COVID-19 is an infectious disease that presents unprecedented challenges to society. Accurately estimating the incubation period of the coronavirus is critical for effective prevention and control. However, the exact incubation period remains unclear, as COVID-19 symptoms can appear in as little as 2 days or as long as 14 days or more after exposure. Accurate estimation requires original chain-of-infection data, which may not be fully available from the original outbreak in Wuhan, China. In this study, we estimated the incubation period of COVID-19 by leveraging well-documented and epidemiologically informative chain-of-infection data collected from 10 regions outside the original Wuhan areas prior to February 10, 2020. We employed a proposed Monte Carlo simulation approach and nonparametric methods to estimate the incubation period of COVID-19. We also utilized manifold learning and related statistical analysis to uncover incubation relationships between different age and gender groups. Our findings revealed that the incubation period of COVID-19 did not follow general distributions such as lognormal, Weibull, or Gamma. Using proposed Monte Carlo simulations and nonparametric bootstrap methods, we estimated the mean and median incubation periods as 5.84 (95% CI, 5.42-6.25 days) and 5.01 days (95% CI 4.00-6.00 days), respectively. We also found that the incubation periods of groups with ages greater than or equal to 40 years and less than 40 years demonstrated a statistically significant difference. The former group had a longer incubation period and a larger variance than the latter, suggesting the need for different quarantine times or medical intervention strategies. Our machine-learning results further demonstrated that the two age groups were linearly separable, consistent with previous statistical analyses. Additionally, our results indicated that the incubation period difference between males and females was not statistically significant.

Symptoms at presentation in conservatively managed patients with non-functioning pituitary adenomas.

PURPOSE: Hypopituitarism and tumor growth are rare in patients with non-functioning pituitary microadenomas (NFPmA). However, patients often present with non-specific symptoms. The aim of this brief report is to examine presenting symptomatology in patients with NFPmA compared to patients with non-functioning pituitary macroadenomas (NFPMA). METHODS: We performed a retrospective review of 400 patients (347 NFPmA and 53 NFPMA) who were conservatively managed; no patients had indications for urgent surgical intervention. RESULTS: Average tumor size was 4.5 ± 1.9 and 15.5 ± 5.5 mm for NFPmA and NFPMA, respectively (p < 0.001). At least one pituitary deficiency was present in 7.5% of patients with NFPmA and 25% of patients with NFPMA. Patients with NFPmA were younger (41.6 ± 15.3 vs. 54.4 ± 22.3 years, p < 0.001) and more commonly female (64.6 vs. 49.1%, p = 0.028). There was no significant difference reported for similarly high rates of fatigue (78.4% and 73.6%), headache (70% and 67.9%), and blurry vision (46.7% and 39.6%). There were no significant differences in comorbidities. CONCLUSION: Despite smaller size and lower rate of hypopituitarism, patients with NFPmA presented with a high prevalence of headache, fatigue, and visual symptoms. This was not significantly different from patients with NFPMA who were conservatively managed. We conclude that symptoms of NFPmA cannot fully be attributed to pituitary dysfunction or mass effect.

Nonfunctioning Pituitary Microadenomas: Should Imaging Interval be Extended? A Large Single-center Cohort Study.

CONTEXT: Characterization of the clinical features and natural history of nonfunctioning pituitary microadenomas (NFPmAs) is limited by heterogeneous and small-scale studies. OBJECTIVE: To characterize the clinical presentation and natural history of NFPmAs and evaluate if imaging follow-up interval can be extended. METHODS: Retrospective single-center cohort study (years 2006-2021) of conservatively managed patients with NFPmAs. Initial symptoms, pituitary function, and tumor size were assessed. A change in NFPmA size ≥2 mm, as determined by pituitary or brain magnetic resonance imaging (MRI), was considered significant. RESULTS: There were 347 patients in the study cohort. Headache (78.4%) and fatigue (70.0%) were commonly reported despite no evidence of mass effect or significant pituitary hypofunction. Pituitary deficiencies at baseline were rare, with hypogonadism being most common (5.1%). During a median imaging follow-up period of 29 months (range 3-154), 8.1% of NFPmAs grew. Growth incidence was 2.1 per 100 person-years with a mean and median time to growth of 38.1 (SD ± 36.4) and 24.5 (interquartile range 12.0-70.8) months, respectively. Tumor growth was mild and not associated with new pituitary deficiencies or visual deficits. CONCLUSION: These data indicate that the natural history of NFPmAs is overall benign. Consequently, we propose that the initial MRI follow-up timeline for NFPmAs can be extended up to 3 years unless a lesion is close to the optic chiasm, there are worrisome mass effect symptoms, or new pituitary deficiencies.

Updates in adrenal steroidogenesis inhibitors for Cushing's syndrome - A practical guide.

Medical therapy is essential in the management of patients with Cushing's syndrome (CS) when curative surgery has failed, surgery is not feasible, when awaiting radiation effect, and in recurrent cases of CS. Steroidogenesis inhibitors have a rapid onset of action and are effective in reducing hypercortisolism, however, adverse effects, including adrenal insufficiency require very close patient monitoring. Osilodrostat is the only steroidogenesis inhibitor to have been assessed in prospective randomized controlled trials and approved for Cushing's disease (CD) by the US Food and Drug Administration and for CS by the European Medical Agency (EMA). Osilodrostat has been shown to be highly effective at maintaining normal urinary free cortisol in patients with CD. Drugs such as metyrapone, ketoconazole (both EMA approved), and etomidate lack prospective evaluation(s). There is, however, considerable clinical experience and retrospective data that show a very wide efficacy range in treating patients with CS. In the absence of head-to-head comparative clinical trials, therapy choice is determined by the specific clinical setting, risk of adverse events, cost, availability, and other factors. In this review practical points to help clinicians who are managing patients with CS being treated with steroidogenesis inhibitors are presented.

Increase in Free and Total Plasma TGF-ß1 Following Physical Activity.

OBJECTIVE: To evaluate effects of physical activity and food consumption on plasma concentrations of free and total transforming growth factor beta-1 (TGF-ß1), beta-2 (TGF-ß2), and beta-3 (TGF-ß3) in individuals with knee osteoarthritis (OA). METHODS: Participants (n = 40 in 2 cohorts of 20; mean age 70 years) with radiographic knee OA were admitted overnight for serial blood sampling. Cohorts 1 and 2 assessed the impacts of food intake and activity, respectively, on TGF-ß concentrations. Cohort 1 blood draws included 2 hours postprandial the evening of day 1 (T3), fasting before rising on day 2 (T0), nonfasting 1 hour after rising (T1B), and 4 hours after rising (T2). Cohort 2 blood draws included T3, T0, fasting 1 hour after rising and performing activities of daily living (T1A), and nonfasting 2 hours after rising (T1B). By sandwich ELISAs, we quantified plasma free and total TGF-ß1 concentrations in all samples, and plasma total TGF-ß2 and TGF-ß3 in cohort 2. RESULTS: Free TGF-ß1 represented a small fraction of the total systemic concentration (mean 0.026%). In cohort 2, free and total TGF-ß1 and total TGF-ß2 concentration significantly increased in fasting samples collected after an hour (T1A) of activities of daily living (free TGF-ß1: P = 0.006; total TGF-ß1: P < 0.001; total TGF-ß2: P = 0.001). Total TGF-ß3 increased nonsignificantly following activity (P = 0.590) and decreased (P = 0.035) after food consumption while resting (T1B). CONCLUSIONS: Increased plasma concentrations of TGF-ß with physical activity suggests activity should be standardized prior to TGF-ß1 analyses.

Distinct chronology of neuronal cell cycle re-entry and tau pathology in the 3xTg-AD mouse model and Alzheimer's disease patients.

Cell cycle re-entry in Alzheimer's disease (AD) has emerged as an important pathological mechanism in the progression of the disease. This appearance of cell cycle related proteins has been linked to tau pathology in AD, but the causal and temporal relationship between the two is not completely clear. In this study, we found that hyperphosphorylated retinoblastoma protein (ppRb), a key regulator for G1/S transition, is correlated with a late marker for hyperphosphorylation of tau but not with other early markers for tau alteration in the 3xTg-AD mouse model. However, in AD brains, ppRb can colocalize with both early and later markers for tau alterations, and can often be found singly in many degenerating neurons, indicating the distinct development of pathology between the 3xTg-AD mouse model and human AD patients. The conclusions of this study are two-fold. First, our findings clearly demonstrate the pathological link between the aberrant cell cycle re-entry and tau pathology. Second, the chronological pattern of cell cycle re-entry with tau pathology in the 3xTg-AD mouse is different compared to AD patients suggesting the distinct pathogenic mechanism between the animal AD model and human AD patients.

Blue lighting decreases the amount of food consumed in men, but not in women.

Previous research has demonstrated that colors of lighting can modulate participants' motivation to consume the food placed under the lighting. This study was designed to determine whether the colors of lighting can affect the amount of food consumed, in addition to sensory perception of the food. The influence of lighting color was also compared between men and women. One-hundred twelve participants (62 men and 50 women) were asked to consume a breakfast meal (omelets and mini-pancakes) under one of three different lighting colors: white, yellow, and blue. During the test, hedonic impression of the food's appearance, willingness to eat, overall flavor intensity and overall impression of the food, and meal size (i.e., the amount of food consumed) were measured. Blue lighting decreased the hedonic impression of the food's appearance, but not the willingness to eat, compared to yellow and white lighting conditions. The blue lighting significantly decreased the amount consumed in men, but not in women, compared to yellow and white lighting conditions. Overall flavor intensity and overall impression of the food were not significantly different among the three lighting colors. In conclusion, this study provides empirical evidence that the color of lighting can modulate the meal size. In particular, blue lighting can decrease the amount of food eaten in men without reducing their acceptability of the food.

Role of reverse micelles on lipid oxidation in bulk oils: impact of phospholipids on antioxidant activity of α-tocopherol and Trolox.

Phospholipids self-assemble in bulk oils to form structures such as reverse micelles that can alter the microenvironment where chemical degradation reactions occur, such as lipid oxidation. In this study, we examined the influence of phospholipid reverse micelles on the activity of non-polar (α-tocopherol) and polar (Trolox) antioxidants in stripped soybean oil (SSO). Reverse micelles were formed by adding 1000 µM 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) to SSO. The addition of DOPC reverse micelles had a prooxidant effect, shortening the lag phase of SSO at 55 °C. DOPC improved the activity of low α-tocopherol or Trolox concentrations (10 µM) but decreased the activity of high concentrations (100 µM). Hydrophilic Trolox had better antioxidant activity than hydrophobic α-tocopherol. Fluorescence steady state and lifetime decay studies suggests that differences in the antioxidant activity of Trolox and α-tocopherol could be due to differences in their physical location in DOPC reverse micelles. These results will improve our understanding and control of lipid oxidation in bulk oils.

Physical structures in soybean oil and their impact on lipid oxidation.

The oxidation of edible oil yields both primary and secondary oxidation products (e.g., hydroperoxides, carbonyls, hydrocarbons, and epoxides), which produce undesirable sensory and biological effects. Consequently, the suppression of lipid oxidation in food matrices is of great importance. The rate and extent of lipid oxidation in many heterogeneous foods are strongly affected by the physicochemical characteristics of water-oil interfaces. This study examined the ability of dioleoylphosphatidylcholine (DOPC) and water to form association colloids within bulk oil, as well as their impact on lipid oxidation kinetics. Attenuation was used to show the DOPC and water concentrations at which association colloids existed without altering the optical properties of the oil. Interfacial tension and fluorescence spectrometry showed the critical micelle concentration (CMC) of DOPC in stripped soybean oil was around 650 µM at room temperature. Small-angle X-ray scattering (SAXS) and fluorescence probes showed that water had a very strong impact on the properties of the association colloids formed by DOPC. Measurement of primary and secondary lipid oxidation products revealed that the association colloids formed by DOPC had a pro-oxidant effect. The characterization of association colloids could provide a better understanding of the mechanisms of lipid oxidation in bulk oils and provide insights into new antioxidant technologies.